MAP kinase-interacting kinases - Emerging targets against cancer

Sarah Diab, Malika Kumarasiri, Mingfeng Yu, Theodosia Teo, Christopher Proud, Robert Milne, Shudong Wang

Research output: Contribution to journalReview article

61 Citations (Scopus)

Abstract

Mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) regulate the initiation of translation through phosphorylation of eukaryotic initiation factor 4E (eIF4E). Mnk-mediated eIF4E activation promotes cancer development and progression. While the phosphorylation of eIF4E is necessary for oncogenic transformation, the kinase activity of Mnks seems dispensable for normal development. For this reason, pharmacological inhibition of Mnks could represent an ideal mechanism-based and nontoxic therapeutic strategy for cancer treatment. In this review, we discuss the current understanding of Mnk biological roles, structures, and functions, as well as clinical implications. Importantly, we propose different strategies for identification of highly selective small molecule inhibitors of Mnks, including exploring a structural feature of their kinase domain, DFD motif, which is unique within the human kinome. We also argue that a combined targeting of Mnks and other pathways should be considered given the complexity of cancer.

Original languageEnglish
Pages (from-to)441-452
Number of pages12
JournalChemistry and Biology
Volume21
Issue number4
DOIs
Publication statusPublished - 24 Apr 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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